Recruiting

Phase 1

Phase 2

Cladribine, Idarubicin, Cytarabine, QuizartinibCladribine, Idarubicin, Cytarabine, and Quizartinib in Treating Patients With Newly Diagnosed, Relapsed, or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

Sponsor:

M.D. Anderson Cancer Center

Code:

NCT04047641

Conditions

Acute Myeloid Leukemia

Blasts 20 Percent or More of Bone Marrow Nucleated Cells

High Risk Myelodysplastic Syndrome

Recurrent Acute Biphenotypic Leukemia

Recurrent Acute Myeloid Leukemia

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Cladribine

Cytarabine

Idarubicin

Quizartinib

Study Details

Brief summary:

This phase I/II trial studies the side effects and how well cladribine, idarubicin, cytarabine, and quizartinib work in treating patients with acute myeloid leukemia or high-risk myelodysplastic syndrome that is newly diagnosed, has come back (relapsed), or does not respond to treatment (refractory). Drugs used in chemotherapy, such as cladribine, idarubicin, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Quizartinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving quizartinib with cladribine, idarubicin, and cytarabine may help to control acute myeloid leukemia or high-risk myelodysplastic syndrome.

Conditions

Acute Myeloid Leukemia

Blasts 20 Percent or More of Bone Marrow Nucleated Cells

High Risk Myelodysplastic Syndrome

Recurrent Acute Biphenotypic Leukemia

Recurrent Acute Myeloid Leukemia

Study ID

NCT04047641

Start date

Oct 22, 2019

Status verified date

Jun, 2026

Completion date

Dec 31, 2027

Anticipated

Primary completion date

Dec 31, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Diagnosis of

AML (World Health Organization \[WHO\] classification definition of >= 20% blasts, excluding Acute promyelocytic leukemia),
Acute biphenotypic leukemia or
High-risk MDS (> 10% bone marrow blasts)
Frontline cohort: Patients aged 18 to 65 years
Relapse cohort: Patients aged >=18 years old
Patients may be newly diagnosed (Frontline cohort) or with prior therapy (Relapsed cohort) as follows:

For frontline cohort: Patients must be chemonaive, i.e., not have received any chemotherapy (except hydroxyurea \[Hydrea\] \[no dose limit\], tretinoin \[atra\] \[no dose limit\] or ara-C \[one or two doses (max 2 gr/m\^2 per dose)\] for transient control of hyperleukocytosis) for AML or MDS. They may have received hypomethylating agents for prior MDS and transfusions, hematopoietic growth factors or vitamins. Temporary prior measures such as apheresis or Hydrea are allowed
For relapsed cohort: Patients with previously treated, relapsed or refractory AML, acute biphenotypic leukemia or high-risk MDS (> 10% bone marrow blasts)
Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Creatinine < 1.5 mg/dl
Total bilirubin < 1.5 mg/dL, unless increase is due to hemolysis or congenital disorder
Transaminases (serum glutamate pyruvate transaminase \[SGPT\]) < 2.5 x upper limit of normal (ULN)
Potassium, magnesium, and calcium (normalized for albumin) levels should be at least within institutional normal limits
Ability to take oral medication
Ability to understand and provide signed informed consent
Baseline test of left ventricular ejection fraction >= 50%
Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 7 days
WOCBP must use appropriate method(s) of contraception such as oral contraceptive pills (OCP), birth control shots, intrauterine device (IUD) etc. WOCBP should use an adequate method to avoid pregnancy until 30 days after the last dose of investigational drug. Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential. Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile) as well as men with known azoospermia do not require contraception
Patients with isolated extramedullary myeloid neoplasm will be eligible

Exclusion Criteria:

Any coexisting medical condition that in the judgment of the treating physician is likely to interfere with study procedures or results
Breastfeeding women
Patients with current active malignancies or any remission for < 6 months, except patients with carcinoma in situ or with non-melanoma skin cancer who may be in remission for less than 6 months or have active disease
Active clinically serious and uncontrolled infection. Patients with recent infections must have no temperature of >= 101 degrees Fahrenheit (F) for at least 48 hours (hrs) (before first dose, day 1)
Patients with known significant impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of quizartinib
Documented active central nervous system leukemia (patients with history of central nervous system \[CNS\] leukemia without active disease are allowed)
Patients with a known confirmed diagnosis of human immunodeficiency virus (HIV) infection or active viral hepatitis
Patients who have had any major surgical procedure within 14 days of day 1
Impaired cardiac function including any of the following:

Screening electrocardiography (ECG) with a corrected QT (QTc) > 450 msec. The QTc interval will be calculated by Fridericia's correction factor (QTcF). The QTcF will be derived from the average QTcF in triplicate. Patients are excluded if they have QTcF >= 450. Subjects with prolonged QTcF interval in the setting of RBBB (right bundle branch block) may participate upon review and approval by the medical monitor. RBBB for patients' triplicate electrocardiograms (EKGs) can show false QTc prolongation; therefore, the cardiology collaborator for this study will manually review to provide an accurate reading of the QTc
Patients with congenital long QT syndrome
Sustained ventricular tachycardia requiring medical intervention
Any history of clinically significant ventricular fibrillation or torsades de pointes
Known history of second or third degree heart block (may be eligible if the patient currently has a pacemaker)
Heart rate of < 50/minute on pre-entry ECG
Left bundle branch block
Right bundle branch block + left anterior hemiblock (bifascicular block)
Patients with myocardial infarction or unstable angina within 6 months prior to starting study drug
Congestive heart failure (CHF) New York (NY) Heart Association class III or IV
Atrial fibrillation documented within 2 weeks prior to first dose of study drug
Known family history of congenital long QT syndrome
Patients who are actively taking a strong CYP3A4 inducing medication

Study Design

Enrollment

80 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (idarubicin, cladribine, cytarabine, quizartinib)

INDUCTION: Patients receive idarubicin Intravenous over 1 hours on days 1-3, cladribine intravenous over 1-2 hours on days 1-5, cytarabine Intravenous over 3 hours on days 1-5 (or days 1-3 for patients over age 60), and quizartinib by mouth daily on days 6-19. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Patients who achieve CR or CRp after Induction receive idarubicin Intravenous over 1 hours on days 1-2, cladribine Intravenous over 1-2 hours on days 1-3, cytarabine Intravenous over 3 hours on days 1-3, and quizartinib by mouth daily on days 4-28. Treatment repeats every 28 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients who achieve CR or CRi/CRh after Consolidation receive quizartinib by mouth daily on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Interventions

Cladribine

Given Intravenous

Cytarabine

Given Intravenous

Idarubicin

Given Intravenous

Quizartinib

Given by mouth

Primary outcome measure

Event free survival (EFS) [ Time Frame: From the date of start of treatment until event (resistance or relapse) or death, whichever occurred first, assessed up to 12 months ]
Incidence of adverse events [ Time Frame: Up to 12 months ]

Central Contacts and Locations

Central contacts

Musa Yilmaz

713-794-5783 myilmaz@mdanderson.org

Locations

M D Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Musa Yilmaz

713-794-5783

Principal Investigator:

Musa Yilmaz

More Information

Sponsor

M.D. Anderson Cancer Center

Last update posted

Jun 12, 2026

Last verified

Jun, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by M.D. Anderson Cancer Center on 2026-06-12.